Tautomers Of Nucleic Acid Bases Research Articles

Role of tautomerism in RNA biochemistry.

Heterocyclic nucleic acid bases and their analogs can adopt multiple tautomeric forms due to the presence of multiple solvent-exchangeable protons. In DNA, spontaneous formation of minor tautomers has been speculated to contribute to mutagenic mispairings during DNA replication, whereas in RNA, minor tautomeric forms have been proposed to enhance the structural and functional diversity of RNA enzymes and aptamers. This review summarizes the role of tautomerism in RNA biochemistry, specifically focusing on the role of tautomerism in catalysis of small self-cleaving ribozymes and recognition of ligand analogs by riboswitches. Considering that the presence of multiple tautomers of nucleic acid bases is a rare occurrence, and that tautomers typically interconvert on a fast time scale, methods for studying rapid tautomerism in the context of nucleic acids under biologically relevant aqueous conditions are also discussed.

Combinatorial-computational-chemoinformatics (C3) approach to finding and analyzing low-energy tautomers.

Finding the most stable tautomer or a set of low-energy tautomers of molecules is critical in many aspects of molecular modelling or virtual screening experiments. Enumeration of low-energy tautomers of neutral molecules in the gas-phase or typical solvents can be performed by applying available organic chemistry knowledge. This kind of enumeration is implemented in a number of software packages and it is relatively reliable. However, in esoteric cases such as charged molecules in uncommon, non-aqueous solvents there is simply not enough available knowledge to make reliable predictions of low energy tautomers. Over the last few years we have been developing an approach to address the latter problem and we successfully applied it to discover the most stable anionic tautomers of nucleic acid bases that might be involved in the process of DNA damage by low-energy electrons and in charge transfer through DNA. The approach involves three steps: (1) combinatorial generation of a library of tautomers, (2) energy-based screening of the library using electronic structure methods, and (3) analysis of the information generated in step (2). In steps 1–3 we employ combinatorial, computational and chemoinformatics techniques, respectively. Therefore, this hybrid approach is named “Combinatorial*Computational*Chemoinformatics”, or just abbreviated as C3 (or C-cube) approach. This article summarizes our developments and most interesting methodological aspects of the C3 approach. It can serve as an example how to identify the most stable tautomers of molecular systems for which common chemical knowledge had not been sufficient to make definite predictions.

Gas phase interaction of zinc ion with purine and pyrimidine DNA and RNA bases

AbstractThe interaction of uracil, thymine, cytosine, adenine, and guanine with zinc ion was studied at the density functional B3LYP/6‐311+G(2df,2p) level. Different binding sites allowing both mono‐metal and bi‐metal coordination were considered for the different low‐lying tautomers of nucleic acid bases. Zinc ion forms stable compounds with all nucleobases. Except for cytosine, mono‐coordination appears to be less favored than bi‐coordination in the other pyrimidines. Instead, the preferred sites in the case of adenine and guanine were found to be the N7 and O6 and N7 and N6 pairs of atoms, respectively. Zinc ion affinity was evaluated for all the complexes and compared with values previously obtained for other transition metal ions. In the present case, the following order of metal ion affinity (MIA) was found: G>A>C>T>U. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

Comprehensive Study of the Effects of Methylation on Tautomeric Equilibria of Nucleic Acid Bases

Minor tautomers of nucleic acid bases can result by intramolecular proton transfer. These rare tautomers could be stabilized through the addition of methyl groups to DNA bases. A comprehensive theoretical study of tautomers of methylated derivatives of guanine, adenine, cytosine, thymine, and uracil was performed. Molecular geometries of all tautomers were obtained at the density functional theory and MP2 levels with the 6-31G(d,p) basis set, and single-point calculations were performed at the CCSD(T)/6-311G(d,p) level. Tautomers obtained by protonation at the preferred protonation site for methylated isolated bases were compared to their nonmethylated counterparts. The effects of methylation on the relative stabilities of nucleic acid base tautomers are also studied and discussed in this work. The results suggest that some sites on the bases may not be mutagenic and may even stabilize the canonical Watson-Crick form. The results also indicate that a number of methylation sites can stabilize the tautomers, suggesting possible mechanisms for mutagenic changes.

Bond energies and attachments sites of sodium and potassium cations to DNA and RNA nucleic acid bases in the gas phase.

Gas-phase metal affinities of DNA and RNA bases for the Na(+) and K(+) ions were determined at density functional level employing the hybrid B3LYP exchange correlation potential in connection with the 6-311+G(2df,2p) basis set. All the molecular complexes, obtained by the interaction between several low-lying tautomers of nucleic acid bases and the alkali ions on the different binding sites, were considered. Structural features of the sodium and potassium complexes were found to be similar except in some uracil and thymine compounds in which the tendency of potassium ion toward monocoordination appeared evident. B3LYP bond energies for both metal ions were in agreement with the available experimental results in the cases of uracil and thymine for which the most stable complex was obtained starting from the most stable tautomer of the free nucleic acid base. For adenine, although the interaction of the ions with the most stable free tautomer generated the least stable molecular complex, the best agreement with experiment was found in just this case. For the remaining cytosine and guanine bases, our calculations indicated that the metal ion affinity value closest to experiment should be determined taking into account the role played by the different tautomers of the free bases with similar energy and all the possible complexes obtained by them.

Lithium Affinity for DNA and RNA Nucleobases. The Role of Theoretical Information in the Elucidation of the Mass Spectrometry Data

The binding energy and the metalation site of lithium cation for the most stable tautomers of nucleic acid bases were determined by using “hybrid” B3LYP density functional computations. For each isomer of the same base the metal affinity values are very different and depend on the coordination mode of lithium. For thymine and uracil, the experimental indication on the metalation site and on the absolute value of metal affinity agrees with our data. For the remaining bases, the presence of the metal, in some case, gives rise to a complex stability order different from that of naked tautomers. Results in these cases show that there is always only one tautomer whose metal affinity value corresponds to the experimental measurements. This tautomer is not necessarily the most stable one.

ChemInform Abstract: Contributions from Electron Correlation to the Relative Stabilities of the Tautomers of Nucleic Acid Bases.

AbstractDifferent levels of many‐body perturbation theory are used to study the relative stabilities of models of uracil and cytosine tautomers.

Contributions from electron correlation to the relative stabilities of the tautomers of nucleic acid bases

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTContributions from electron correlation to the relative stabilities of the tautomers of nucleic acid basesJozef S. Kwiatkowski, Rodney J. Bartlett, and Willis B. PersonCite this: J. Am. Chem. Soc. 1988, 110, 8, 2353–2358Publication Date (Print):April 1, 1988Publication History Published online1 May 2002Published inissue 1 April 1988https://doi.org/10.1021/ja00216a001RIGHTS & PERMISSIONSArticle Views161Altmetric-Citations111LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (812 KB) Get e-Alerts Get e-Alerts

Experimental and theoretical studies of tautomers of nucleic acid bases

Experimental and theoretical studies of tautomers of nucleic acid bases